We have now completed a six month open trial of the efficiency of Trental (pentoxifylline) in chronic progressive M.S. patients. The trial was based on a report in Lancet that M.S. patients have elevated levels of TNFa in the CSF during the course of their disease and that trental decreases TNFa levels in patients with inflammatory diseases. The study is now completed. We are 1) unable to confirm the report of elevated levels of TNFa in either sera or CSF samples obtained from these patients. 2) Clinical evaluation of these patients over a six month period failed to reveal any improvement in their clinical status. We are continuing our efforts to determine whether a virus might be implicated in the pathogenesis of this disease. Studies extending over the past year have centered around the question of whether any member of the retroviral family might be involved. Using PCR primers specific for both spuma virus and retroviruses, we were unable to find DNA evidence of these viruses in the brains of 23 M.S. patients and an equal number of non-MS neurological controls. Recently a report appeared in PNAS() in which probes specific for Herpes B6 virus detected nucleotide sequences specific for this virus in equal numbers of M.S. and other neurologic disease controls. However, immunohistochemical studies revealed the presence of Herpes B6 viral proteins in the oligodendrocytes of M.S. patients and not in other neurologic controls. Using PCR and appropriate primers, we have confirmed the original data indicating the presence of Herpes B6 DNA in the tissues of M.S. and non-M.S. brains. We are currently examining these tissues immunohistochemically for the presence of Herpes B6 viral products.